Zaaba Nur Elena, Al-Salam Suhail, Beegam Sumaya, Elzaki Ozaz, Aldhaheri Fatima, Nemmar Anas, Ali Badreldin H, Nemmar Abderrahim
Department of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
Department of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
Front Pharmacol. 2025 Apr 2;16:1567888. doi: 10.3389/fphar.2025.1567888. eCollection 2025.
Cisplatin (CP)-induced acute kidney injury (AKI) is a significant side effect of CP chemotherapy, driven by oxidative stress and inflammation. Sanguinarine (SANG), an alkaloid from the rhizomes of Sanguinaria canadensis and poppy-fumaria species, exhibits antioxidant and anti-inflammatory properties. This study examined SANG's effect on CP-induced AKI in mice and its underlying mechanisms.
Mice were orally administered 5 mg/kg SANG for 10 days. On the seventh day, they received a single intraperitoneal CP injection (20 mg/kg) and were sacrificed on the 11th day.
SANG significantly improved CP-induced decreases in body weight, water intake, urine volume, relative kidney weight, creatinine clearance, albumin-to-creatinine ratio, and plasma urea and creatinine levels. It also reduced elevated plasma neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, cystatin C, and adiponectin levels, as well as renal markers of inflammation and oxidative stress induced by CP administration. SANG normalized kidney mitochondrial dysfunction, DNA damage, and apoptosis caused by CP. It also inhibited the CP-induced increase in the expression of phosphorylated nuclear factor-κB and autophagy markers in the kidney. Histological analysis showed that SANG reduced acute tubular necrosis and intraluminal protein accumulation due to CP.
In conclusion, SANG mitigated CP-induced AKI by reducing inflammation, oxidative stress, DNA damage, apoptosis, and autophagy. Pending more comprehensive pharmacological and toxicological assessments, SANG may be regarded as a potential therapeutic agent for mitigating CP-induced AKI.
顺铂（CP）诱导的急性肾损伤（AKI）是CP化疗的一种重要副作用，由氧化应激和炎症驱动。血根碱（SANG）是一种从加拿大血根草和罂粟紫堇属植物根茎中提取的生物碱，具有抗氧化和抗炎特性。本研究考察了SANG对CP诱导的小鼠AKI的影响及其潜在机制。
小鼠口服给予5mg/kg SANG，持续10天。在第7天，它们接受单次腹腔注射CP（20mg/kg），并在第11天处死。
SANG显著改善了CP诱导的体重、饮水量、尿量、相对肾重、肌酐清除率、白蛋白与肌酐比值以及血浆尿素和肌酐水平的降低。它还降低了血浆中升高的中性粒细胞明胶酶相关脂质运载蛋白、肾损伤分子-1、胱抑素C和脂联素水平，以及CP给药诱导的肾脏炎症和氧化应激标志物。SANG使CP引起的肾脏线粒体功能障碍、DNA损伤和细胞凋亡恢复正常。它还抑制了CP诱导的肾脏中磷酸化核因子-κB和自噬标志物表达的增加。组织学分析表明，SANG减轻了CP引起的急性肾小管坏死和管腔内蛋白质积聚。
总之，SANG通过减轻炎症、氧化应激、DNA损伤、细胞凋亡和自噬来减轻CP诱导的AKI。在进行更全面的药理和毒理学评估之前，SANG可被视为减轻CP诱导的AKI的潜在治疗剂。
